Role of 5-HT and BDNF in Premature Ejaculation With Anxiety or Depression

A 2026 narrative review maps how serotonin and BDNF link premature ejaculation to comorbid anxiety and depression — and makes a pitch for TCM adjuncts

Journal: Journal of Integrative Neuroscience | Published: 2026-03-17 | Type: Narrative Review | PMID: 41914255 Authors: Wei Yi, Ning Bo, Wang Shengjie et al. (Guangzhou University of Chinese Medicine; Shenzhen Traditional Chinese Medicine Hospital) Funding/COI: National Natural Science Foundation of China; Shenzhen Science and Technology Program. No conflicts of interest declared.

Summary

This narrative review argues that premature ejaculation (PE) co-occurring with anxiety or depression is mechanistically unified — not two conditions happening at once, but one dysregulated serotonergic and neurotrophic system expressing itself across both reproductive and emotional domains. The authors survey 5-HT and BDNF signaling across ejaculation control, mood regulation, inflammation, and oxidative stress, then pivot to treatment implications. The final section promotes Traditional Chinese Medicine (TCM) formulations as potential stand-alone or adjunctive options to reduce SSRI dependence — a claim that arrives with thin evidentiary support relative to the mechanistic content.

Claims

• 5-HT deficiency and BDNF dysregulation are proposed as shared pathological drivers of both ejaculatory dysfunction and comorbid anxiety/depression
• SSRIs delay ejaculation by blocking serotonin reuptake but carry documented risks; the review calls for individualized dosing and monitoring without specifying what that looks like
• TCM formulations are claimed to "extend intravaginal ejaculatory latency and mitigate mood symptoms" and may reduce reliance on SSRIs — no pooled effect size or trial count provided in the abstract
• Pathological mechanisms reviewed include neurotransmitter imbalance, neuroendocrine dysregulation, inflammation, and oxidative stress

Study Quality

This is a narrative review, not a systematic review or meta-analysis. The literature search covered 2010–2025 across unspecified databases using MeSH terms, but no PRISMA flow diagram, inclusion/exclusion criteria, or quality assessment of included studies is described in the abstract. That makes it impossible to evaluate selection bias or reproducibility. Narrative reviews of this type are useful for hypothesis generation but cannot establish the weight of evidence behind any individual claim.

The institutional affiliation — Guangzhou University of Chinese Medicine and Shenzhen TCM Hospital — creates an obvious framing incentive for the TCM-positive conclusions. The funding sources (Chinese national and municipal science programs) do not directly implicate pharmaceutical or TCM commercial interests, but the institutional context warrants scrutiny of how TCM evidence was weighted against SSRI evidence.

Red Flags

• Narrative review with no stated methodology for study selection — cherry-picking risk is unquantifiable
• TCM efficacy claims appear in the conclusions without a specific trial count, pooled effect size, or comparison to placebo
• No conflict of interest declarations from authors at a TCM-affiliated institution reviewing TCM interventions — absence of disclosure is not the same as absence of interest
• "Individualized dosing and monitoring" for SSRIs is flagged without clinical guidance, which is unusual for a review claiming therapeutic relevance
• Journal of Integrative Neuroscience publishes work across a wide quality range; this paper's conclusions outrun its methodology

Strengths

• The mechanistic framework connecting 5-HT and BDNF across ejaculation control and mood disorders is coherent and grounded in established neuroscience
• Comorbid PE + anxiety/depression is a genuinely undercharacterized clinical phenotype; framing it as a unified neuro-reproductive syndrome is a reasonable conceptual contribution
• Acknowledging SSRI-associated risks (sexual side effects, discontinuation problems) is honest for a paper in this space

Verdict

The neurobiology is interesting; the evidence base for TCM is not established here. This paper reads as mechanistic groundwork with a treatment advocacy conclusion that exceeds what a narrative review can support. The 5-HT/BDNF dual-pathway framing for PE with comorbid mood disorders is worth tracking — if it generates well-designed RCTs, that's the literature to watch. This review itself is not that evidence.